Tyrosinase versus Catechol Oxidase: One Asparagine Makes the Difference

Tyrosinases mediate the ortho‐hydroxylation and two‐electron oxidation of monophenols to ortho‐quinones. Catechol oxidases only catalyze the oxidation of diphenols. Although it is of significant interest, the origin of the functional discrimination between tyrosinases and catechol oxidases has been unclear. Recently, it has been postulated that a glutamate and an asparagine bind and activate a conserved water molecule towards deprotonation of monophenols. Here we demonstrate for the first time that a polyphenoloxidase, which exhibits only diphenolase activity, can be transformed to a tyrosinase by mutation to introduce an asparagine. The asparagine and a conserved glutamate are necessary to properly orient the conserved water in order to abstract a proton from the monophenol. These results provide direct evidence for the crucial importance of a proton shuttle for tyrosinase activity of type 3 copper proteins, allowing a consistent understanding of their different chemical reactivities.     

Exploring Green Chemistry,Sustainable Chemistry and innovative business models such as Chemical Leasing in the context of international policy discussions

This article provides an overview on Green Chemistry and Sustainable Chemistry in the context of the 2030 Agenda for Sustainable Development and different policy frameworks such as the EU Circular Economy Action Plan and SAICM, the Strategic Approach of International Chemicals Management. There is an increasing body of evidence suggesting the practicality and applicability of Green Chemistry and Sustainable Chemistry within industrial development policies and international agreements addressing chemicals and waste concerns. To explore the full potential of Green Chemistry and Sustainable Chemistry, the authors come to the conclusion that innovative business models are required to facilitate the engagement of the different players, including industry. While presenting the United Nations Industrial Development Organization (UNIDO)’s experiences and lessons learnt from ten years of work in UNIDO's Global Chemical Leasing Programme, the article also highlights the role that innovative and circular economy business models could play in achieving inclusive and sustainable economic growth. It therefore explores the potential of integrated Chemical Leasing, Green Chemistry and Sustainable Chemistry initiatives at the global level.     

A Photoswitchable Dualsteric Ligand Controlling Receptor Efficacy

The investigation of the mode and time course of the activation of G-protein-coupled receptors (GPCRs), in particular muscarinic acetylcholine (mACh or M) receptors, is still in its infancy despite the tremendous therapeutic relevance of M receptors and GPCRs in general. We herein made use of a dualsteric ligand that can concomitantly interact with the orthosteric, that is, the neurotransmitter, binding site and an allosteric one. We synthetically incorporated a photoswitchable (photochromic) azobenzene moiety. We characterized the photophysical properties of this ligand called BQCAAI and investigated its applicability as a pharmacological tool compound with a set of FRET techniques at the M₁ receptor. BQCAAI proved to be an unprecedented molecular tool; it is the first photoswitchable dualsteric ligand, and its activity can be regulated by light. We also applied BQCCAI to investigate the time course of several receptor activation processes.